GOUT therapeutics Flashcards

Question

what causes reduced renal excretion of uric acid?

Answer 1

–reduced tubular uric acid secretion, which may have a genetic component –renal failure –drugs that compete for the tubular transporter for uric acid e.g. diuretics, ciclosporin –Low-dose aspirin also reduces uric acid excretion, but the effect is probably clinically insignificant

Answer 2

``` precipitation of urate crystals in joint 1- activation of complement and kinin system neutrophil chemotaxis phagocytosis of crystals by neutrohils lysis of neutrophils release of lysosomonal enzymes tissue injury and inflamation or release or LTB4 prostaglandings, free radicals ``` - phagocytosis by macrophages release of il1 , other cytokines neytrophil chemotaxis....

Answer 3

1. Asymptomatic Gout 2. Acute “gouty arthritis” –Swollen joint with inflammation –Pyrexia and erythematous –Caused by uric acid in the joint –Gout ‘flares’ 3. Asymptomatic inter-critical period 4. Chronic tophaceous gout –After ~ 10 years –Occurrence of Tophi –May affect other surrounding tissues

Answer 4

region of chronic foreign body granulomatous | response surrounding collections of MSU crystals

Answer 5

``` •Physician observation •X-Ray, ultrasound •Lab tests –Serum Uric Acid (SUA) –CRP C-Reactive Protein –ESR •Gold Standard - MSU crystal detection in synovial fluid aspirates •Rule out infection, tumours etc •CVD and Renal tests ```

Answer 6

•Prophylactic treatment –Xanthine oxidase inhibitors –Uricosuric drugs –Uricase's •Symptomatic treatment –Colchicine –Corticosteroids –Nonsteroidal anti-inflammatory agents •Lifestyle modifications

Answer 7

•NSAIDs – diclofenac, Indomethacin, Naproxen, Piroxicam in conjunction with PPIs if necessary •Etoicoxib – COX2 inhibitor licensed for Gout management •Corticosteroids - Presnisolone RICE

Answer 8

Second line – Colchicine, especially is NSAIDs | contraindicated

Answer 9

Colchicine modulates multiple pro- and anti- inflammatory pathways associated with gouty arthritis

Answer 10

Colchicine prevents microtubule assembly and disrupts inflammasome and neutrophil activation •Prevents microtubule-based inflammatory cell chemotaxis, generation of leukotrienes and cytokines, and phagocytosis impacting pain and inflammation

Answer 11

PMNs release inflammatory leukotrienes that attract inflammatory cells •Colchicine acts on microtubules in the inflammatory cells •NSAIDs act on cyclooxygenase-2 (COX II) in all of the cells of the joint

Answer 12

urare lowering therapies0 inhibit uric acid synthesis

Answer 13

Allopurinol inhibits Xanthine Oxidase

Answer 14

Allopurinol is first converted to | Alloxanthine

Answer 15

``` Allopurinol reduces the concentration uric acid in all tissues •Increases the more soluble precursors - xanthines and hypoxanthines. •The deposition of urate crystals in tissues (tophi) is reversed ```

Answer 16

Allopurinol is given orally and is well absorbed. Its half-life is 2–3 h: its active metabolite alloxanthine has a half-life of 18–30 h. Renally excreted

Answer 17

–Gastrointestinal disturbances, –allergic reactions (mainly rashes) –toxic epidermal necrolysis and Stevens–Johnson syndrome are rare

Answer 18

during an accute attack Acute attacks of gout occur commonly during the early stages of therapy so treatment with allopurinol is never initiated during an acute attack and is usually combined with an NSAID initially.

Answer 19

is an alternative inhibitor which has a similar pharmacology and MOA as Allopurinol - Xanthine Oxidase inhibitor

Answer 20

Allopurinol is FIRST choice and give Febuxostat if allopurinol not tolerated

Answer 21

increase uric acid excretion by a direct action on the renal tubule

Answer 22

3rd line - Useful for prophylaxis for patients with severe recurrent gout who have severe adverse reactions to allopurinol. Treatment with uricosuric drugs is initiated together with an NSAID

Answer 23

Several transporter proteins have been proposed to participate in uric acid reabsorption e.g. URAT1 and GLUT9

Answer 24

–Probenecid – popular until allopurinol developed –Benzbromarone – potent but reports of hepatotoxicity –Lesinurad – URAT1 inhibitor

Answer 25

* Inhibition of Urate transporters prevent reabsorption * Increase renal excretion * Decrease in Uric acid / Urate levels in serum

Answer 26

Competitively inhibits IL-1 binding to the interleukin-1 type I receptor expressed in a wide variety of tissues and organs •Used in patients with rheumatoid arthritis have elevated levels of IL-1

Answer 27

Rasburicase, a preparation containing the enzyme uric acid oxidase, is sometimes used for aggressive treatment of gout. •Oxidises uric acid in the blood to allantoin, which is more soluble and thus more readily excreted.